Phase 1 clinical program for PXL770 was observed to have a
favorable pharmacokinetic, tolerability and safety profile

PXL770 was observed to have a favorable cardiac safety profile in
both healthy subjects and in animal models

PXL770 was observed to show efficacy in adiet-induced
obese-NASH mice model

LYON, France--(BUSINESS WIRE)--
POXEL
SA (Euronext: POXEL - FR0012432516), a biopharmaceutical company
focused on the development of innovative treatments for metabolic
disorders, including type 2 diabetes and non-alcoholic steatohepatitis
(NASH), today announced the presentation of PXL770 data at AMPK - From
Mechanisms to New Therapies Scientific Congress held in
Niagara-on-the-Lake, Ontario, Canada, September 30 - October 4, 2018.
The PXL770 results were presented in two poster presentations and an
oral presentation. The data presented emphasized the favorable
pharmacokinetic, tolerability and safety profile of PXL770 in the Phase
1 program as well as a favorable cardiac and electrocardiography (ECG)
safety profile in both healthy subjects and animal models. In addition,
mechanistic and efficacy data in a diet-induced obese (DIO)-NASH mouse
model were also presented. Poxel previously announced data results from
the Phase 1b multiple ascending dose trial and a drug-drug interaction
study of PXL770, a direct adenosine monophosphate-activated protein
kinase activator (AMPK), in a press
release on July 18, 2018. Based on these results, the Company is
advancing PXL770 into a Phase 2a proof-of-concept study in nonalcoholic
fatty liver disease (NAFLD) patients who likely have NASH in early 2019.

“We are very pleased to have the opportunity to present the complete
data results from our Phase 1 program to the scientific AMPK community
and key experts. AMPK is a major regulator of energy metabolism and its
activation is expected to show beneficial effects in metabolic and
cardiovascular diseases,” said Sophie Bozec, PhD, Senior Vice President,
Research and Development Pharmacology at Poxel. “Supported by positive
preclinical mechanistic and efficacy results in a DIO-NASH model, we
believe that PXL770 is uniquely positioned to treat the underlying root
causes of fatty liver diseases, including liver steatosis, inflammation
and fibrosis, as well as provide benefits for co-morbidities, including
those related to cardiovascular disease.”

“We are looking forward to advancing PXL770 into a Phase 2a
proof-of-concept program for NASH in early 2019,” said Thomas Kuhn, CEO
of Poxel. “With our recent acquisition of DeuteRx’s drug candidate,
PXL065, we are rapidly expanding our presence in NASH and are one of
only a few biotech companies with two clinical programs in development
in this therapeutic area. The underlying pathophysiological mechanisms
that contribute to the development and progression of NAFLD and NASH are
highly complex and support the need for the development of novel
therapies acting on different targets. Both of our programs have the
potential to be developed as a monotherapy or in combination together or
with other agents.”

In a poster presentation, results from the two Phase 1 studies including
single and multiple ascending dose administrations of PXL770
investigated in healthy male subjects (n=124), were presented. The
safety profile was good across the dose range tested with no serious
adverse events nor adverse effects leading to discontinuation. A good
tolerability profile was also observed up to the highest dose tested of
500 mg, both as single or multiple administrations, with no changes in
the electrocardiogram observed. The maximum tolerated dose was not
reached. Pharmacokinetic assessment demonstrated that PXL770 plasma
exposure (Cmax and AUC) increased in a dose dependent manner following
single administration. After multiple administrations, the
pharmacokinetics (Cmax and AUC) of PXL770 were shown to be linear with a
trend for saturation at the highest dose tested. These results suggest
that PXL770 is well positioned to enter Phase 2 development.

In a second poster presentation, cardiac safety was evaluated in an
extensive in vivo program. A pharmacological study performed in a
rat model demonstrated that PXL770 administration (75 mg/kg bid) did not
induce cardiac hypertrophy after 16 weeks of treatment in toxicological
studies and no adverse effects of cardiac hypertrophy or accumulation of
glycogen in the myocardium were detected at 1000 mg/kg dosing during 13
weeks of PXL770 treatment. These results were replicated in the 13-week
treatment study in dogs with no increase in cardiac glycogen content
(Shiff periodic acid staining) observed. A twenty-four-hour Holter-ECG
recording performed in the 13-week study in dogs showed no rhythm or
conduction disorders. Lastly, regulatory safety pharmacological studies
(hERG binding assay, hERG voltage clamp assay and radiotelemetry in
dogs) dedicated to cardiac assessment (cardiac repolarization and
electrocardiographic parameters, blood pressure) did not raise any
safety concerns. The favorable cardiac safety is reinforced by the
absence of adverse effects observed on extensive ECG recordings after a
shorter period of PXL770 administration in healthy subjects evaluated in
the Phase 1 program.

In addition, an oral presentation summarizing PXL770 and its preclinical
profile as a direct AMPK activator, specifically in a diet-induced (high
fat, fructose and cholesterol for 45 weeks) obesity NASH (DIO-NASH)
mouse model, was presented. The results highlighted the beneficial
effect of AMPK activation in the NASH model and the potential of PXL770
as a promising novel treatment option in NAFLD and, in particular, NASH
acting on the three main characteristics of the physiopathology:
steatosis, inflammation and fibrosis.

The posters titled “PXL770, a direct AMPK activator, shows a favorable
cardiac safety profile” and “PXL770, a direct AMPK activator for the
treatment of NASH, shows a favorable PK, tolerability and safety profile
in humans” are available on the Company’s website under “Posters” or by
using the following link http://www.poxelpharma.com/en_us/product-pipeline/posters.

About NASHNon-alcoholic steatohepatitis (NASH) is a
metabolic disease with no clear disease origin that is quickly becoming
a worldwide epidemic. It is characterized by the accumulation of fat in
the liver causing inflammation and fibrosis. The disease can be silent
for a long period of time, but once it accelerates, severe damage and
liver cirrhosis can occur, which can significantly impact liver function
or can even result in liver failure or liver cancer. Typical risk
factors for NASH include obesity, elevated levels of blood lipids (such
as cholesterol and triglycerides) and diabetes. Currently no curative or
specific therapies are available.

About PXL770PXL770 is a first-in-class direct adenosine
monophosphate-activated protein kinase (AMPK) activator. AMPK is a
central regulator of multiple metabolic pathways leading to the control
of lipid metabolism, glucose homeostasis and inflammation. Based on its
central metabolic role, targeting AMPK offers the opportunity to pursue
a wide range of indications to treat chronic metabolic diseases,
including diseases that affect the liver, such as non-alcoholic
steatohepatitis (NASH).

About Poxel SAPoxel uses its development expertise in
metabolism to advance a pipeline of drug candidates focused on the
treatment of metabolic disorders, including type 2 diabetes and
non-alcoholic steatohepatitis (NASH). We have successfully completed the
Phase 2 clinical program for our first-in-class lead product, Imeglimin,
which targets mitochondrial dysfunction, in the U.S., Europe and Japan.
Together, with our partner Sumitomo Dainippon Pharma, we are conducting
the Phase 3 Trials of IMeglimin for Efficacy and Safety (TIMES) program
for the treatment of type 2 diabetes in Japan. Our partner Roivant
Sciences is responsible for Imeglimin’s development and
commercialization in countries outside of Poxel’s partnership with
Sumitomo Dainippon Pharma, including the U.S. and Europe. PXL770, a
first in class direct adenosine monophosphate-activated protein kinase
(AMPK) activator, is advancing into a Phase 2a proof-of-concept program
for the treatment of NASH. PXL770 could also have the potential to treat
additional metabolic diseases. PXL065 (deuterium-stabilized
R-pioglitazone), a mitochondrial pyruvate carrier (MPC), is in Phase 1
and being developed for the treatment of NASH. Poxel also has additional
earlier-stage programs, including deuterated drug candidates for
metabolic, specialty and rare diseases. We intend to generate further
growth through strategic partnerships and pipeline development.
(Euronext: POXEL, www.poxelpharma.com)